The c‐kit proto‐oncogene encodes a tyrosine kinase receptor for stem cell factor and plays a critical role in the growth and differentiation of various types of cells including hematopoietic stem cells. To investigate the mechanisms of its transcriptional regulation, we isolated the 5’flanking region of the human c‐kit gene and characterized its promoter activity in hematopoietic cells. Nucleotide sequence analysis revealed that the 1.2 kb 5’flanking region lacked a typical “TATA box,” but had a relatively high G + C content and four potential Sp1‐binding sites. Putative binding sites for AP‐2, basic helix‐loop‐helix proteins, Ets‐domain proteins, Myb and GATA‐1 were also found. Primer extension and S1 nuclease protection analyses of hematopoietic cells indicated that the major transcription start sites are 62 bp and 58 bp upstream of the translation start site. Essentially the same start sites were detected in non‐hematopoietic cells such as small cell lung carcinoma and glioblastoma: this single promoter in c‐kit is different from the multiple promoter system of c‐fms, a c‐kit‐related gene, in which at least two promoters are differently used in hematopoietic and non‐hematopoietic cells. An analysis of the c‐kit 5’flanking region using the bacterial chloramphenicol acetyltransferase gene (CAT assay) in human erythroleukemia HEL cells, which express the endogenous c‐kit mRNA at high levels, showed that a region from ‐180 to ‐22 is important for the expression of the c‐kit gene. In addition, a negative regulatory element(s) is suggested to be involved in the regulation of the c‐kit gene expression in mammals.
No optimum treatment of iatrogenic immunodeficiency-associated lymphoproliferative disorders due to methotrexate in patients with rheumatoid arthritis (MTX-LPD) has yet been established, although MTX withdrawal is known to have a substantial effect on tumor regression. Here, we retrospectively analyzed 20 cases of MTX-LPD. Tumor shrinkage occurred in 18 of 20 cases, but only following MTX withdrawal. This tumor regression ratio was considerably better than in previous reports, and appeared due to longer "watchful waiting." Lymphocyte recovery at 2 weeks after MTX withdrawal was significantly higher in cases with tumor regression in 1 month than in those without tumor regression (p = 0.001). Median time to maximal efficacy after MTX cessation in cases without chemotherapy was 12 weeks (range 2-76). In conclusion, watchful waiting for a longer period after MTX cessation with observation of early lymphocyte recovery and uninterrupted continuation of other anti-rheumatoid drugs may be an acceptable management plan for MTX-LPD.
CSF overproduction caused by bilateral choroid plexus papillomas can result in hydrocephalus. Radical resection of the bilateral ventricular lesions should be considered for this entity. Thorough evaluation of the surgical specimen is recommended because histological examination of only the lobular surface of the choroid plexus lesion may fail to identify choroid plexus neoplasm.
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